There are two major types of immunity that protect people from infection: humoral immunity which is mediated by antibody-producing B-lymphocytes; and cell-based immunity which is mediated by T-lymphocytes. For many years, it was thought that peptides were the only important targets for T-cells. However, it has recently become apparent that T cells also recognize an array of lipids and glycolipids that are found on the membranes of altered mammalian cells (e.g., neoplastic cells) and microbial pathogens (such as the microorganism responsible for tuberculosis).
As with proteins, there are “antigen presenting cells” (APCs) that process lipids and display antigenic segments on their membrane surfaces. These antigenic segments are held in place by “CD1” proteins which, together with antigen, form a complex that is recognized by CD1-restricted T-cells including NKT (Brigl et al., Annu. Rev. Immunol. 22:817-90 (2004)). Upon binding to such a complex, the T-cells become activated and initiate an immune response by producing pro-inflammatory cytokines, stimulating antibody-producing B cells or directly killing the target APC. From a therapeutic standpoint, one advantage of the CD1 pathway of antigen presentation is that it is the same from person to person. Thus, in contrast to peptide antigens, an immune treatment that is based on lipid antigens should work for everyone.
Recently, saposins were shown to mediate an important step in antigen presentation by participating in the transfer of lipid antigens to CD1 molecules in lysosomes (Kang et al., Nat. Immunol. 5:175-81 (2004); Winau et al., Nat. Immunol., 5:169-74 (2004); Zhou et al., Science 303-523-7 (2004)). However, apart from this, the mechanisms by which lipid antigens are delivered to APCs and transferred to CD1 are poorly understood. A better understanding of this process may lead to the development of improved vaccines and to new methods for treating cancer and autoimmune diseases.